Correspondence Clinical Letter
Clinical Letter Lichen striatus histopathologically mimicking mycosis fungoides
DOI: 10.1111/ddg.12408
Dear Editors, A skin biopsy taken from the right arm of a 1-year-old girl was submitted with very limited clinical information and no pictures. The biopsy revealed a dense band-like infiltrate composed mainly of small and medium-sized lymphocytes within
a slightly fibrotic papillary dermis, associated with prominent exocytosis of lymphocytes, some of which aligned along the basal membrane, and with presence of intra-epidermal vesicles (Figure 1a–c). The infiltrate involved the mid and deep dermis, forming lymphoid nodules located mainly around hair follicles and eccrine glands, and only focally extended to the subcutaneous tissue. The lymphocytes were positive for CD2, CD3 (Figure 1d–f), CD5, and CD7, with a prevalence of CD8+ cytotoxic T cells compared to CD4+ helper T cells. Loss of T-cell antigens (CD2, CD3, CD5) was not observed. The deep nodular lymphoid infiltrate contained large clusters of B cells. In addition, a focal positivity for CD1a (Figure 1g–i) and negativity for CD117 were observed. A provisional diagnosis of cutaneous lymphoproliferative disorder/suspicion of
Figure 1 Biopsy revealed a band-like lymphocytic infiltrate in the upper dermis and a dense perifollicular infiltrates of lymphocytes in the medium and deep dermis (H&E, 25 x) (a); thickened epidermis, with prominent lymphocytic exocytosis and vesiculation coupled with a band-like infiltrate of lymphocytes in the papillary dermis (H&E, 100 x) (b); prominent lymphocytic exocytosis and small vesicles (H&E, 200 x) (c); immunostaining for CD3 highlighted the predominance of T cells (CD3, 25 x) (d); band-like subepidermal infiltrate composed mainly of T cells (CD3, 100 x) (e); marked exocytosis of T cells (CD3, 200 x) (f); immunostaining for CD1a showed the presence of several Langerhans cells (g: CD1a, 25 x; h: CD1a, 100 x) (g–h); some Langerhans cells within epidermal vesicles (CD1a, 200 x) (i).
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© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1211
Correspondence Clinical Letter
Figure 2 1-year-old girl with erythematous papules arranged in a linear distribution expanding to form a long band (a); details of the papules (b).
mycosis fungoides (MF) was made. The need for a close correlation with the clinical history and appearance of the lesions was mentioned in the histologic report. In the meantime, the child was referred to our clinic. She had small pruritic papules, from 0.5 to 1.5 cm in diameter, arranged to form a long band on her arm (Figure 2a–b). She was otherwise well. The clinical features were sufficiently characteristic to allow a definitive diagnosis of lichen striatus (LS) with unusual dense inflammatory infiltrates. This diagnosis was confirmed by an expert external dermatopathologist (LC). T-cell receptor (TCR) gene rearrangement analysis was made. It resulted in a polyclonal pattern. The patient was followed-up every three months and only after 18 months the lesion showed signs of resolution.
Discussion LS is a rare self-limiting inflammatory disorder predominantly of arms, legs and shoulders that occurs particularly in children [1, 2]. It presents as multiple papules, mostly asymptomatic, arranged linearly along the lines of Blaschko [3]. Most cases resolve spontaneously within a few months; few cases with a prolonged phase of activity may persist for two to three years before resolution [4]. Although it should be distinguished clinically from linear nevi and other chronic inflammatory dermatosis following the lines of Blaschko, including psoriasis, lupus erythematous and morphea, the diagnosis generally relies on clear-cut clinical presentation [5]. However, a skin biopsy may rarely be required in unclear cases. Histology is usually non-diagnostic, showing a mild band-like inflammatory infiltrate of lymphocytes
and histiocytes within the papillary dermis with epidermal acanthosis and parakeratosis, and exocytosis of lymphocytes [1]. The infiltrate may be quite dense and distributed around eccrine glands and vessels. Small intraepidermal vesicles containing lymphocytes and Langerhans cells may be present. Sometimes these lesions may display striking overlapping histopathologic features with lichen nitidus, lichen planus, lichen aureus, lichenoid drug eruptions and MF. In children, MF shows more frequently hypopigmented or pityriasis lichenoides-like lesion, but rarely can present as a linear eruption [6–8]. Histopathologically MF is characterized by the presence of a band-like infiltrate within the papillary dermis, composed of monomorphous lymphoid cells with a different degree of atypia. On many occasions, in early patch MF, small lymphocytes predominate and atypical cells are uncommonly seen [6]. Epidermotropism of lymphocytes can be observed in different forms, including lymphocytes aligned along the basal layer of the epidermis and the formation of Pautrier microabscesses [6]. Neoplastic lymphocytes in MF generally show a CD3+ CD4+, CD8- phenotype [6]. Loss of pan-T markers expression can be observed, but it is very rare in early MF [6]. However, especially in pediatric MF a prevalence of CD8+ cytotoxic T-cells represents a common finding [6, 9]. In our patient, the presence of a dense, band-like infiltrate with prominent exocytosis of lymphocytes with a CD8+ phenotype led to a provisional diagnosis of MF, and a confident diagnosis of LS could be made only upon correlation with the clinical picture. TCR gene rearrangement analysis result was in agreement with the diagnosis of benign inflammatory disorder [10].
© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1211
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Correspondence Clinical Letter
LS may present several overlapping histopathologic features with MF [11], and at times the two conditions may be indistinguishable. The band-like infiltrate with intra-epidermal collections of CD8+ cells, and the lymphoid infiltrate around the follicles within the mid-dermis were erroneously interpreted as features of cytotoxic MF. Although MF may exceptionally present with a linear eruption of small vesicles, in our case the typical clinical presentation and absence of other manifestations of the disease at follow-up allow making a confident diagnosis of LS. We find this case of LS instructive because of the remarkable histopathological similarities to MF and the prolonged phase of activity, representing pitfalls in the clinicopathologic diagnosis. The knowledge of the broad spectrum of histopathologic presentation of LS is essential in dermatopathological practice, especially to exclude a diagnosis of MF. As a general rule, a diagnosis of MF in children should be made, particularly in children, only by integration of complete clinical information and pictures, and morphologic and phenotypic studies, supplemented, in more ambiguous lymphoid proliferation, by molecular approaches; a misdiagnosis, particularly in this age group, may be associated with unnecessary aggressive treatment and disastrous consequences for the patients. Conflict of interest None.
Massimo Mascolo1, Daniela Russo1, Massimiliano Scalvenzi2, Pierpaolo Di Lorenzo3, Lorenzo Cerroni4 (1) Department of Advanced Biomedical Sciences, Pathology Section, University of Naples Federico II, Naples, Italy (2) Department of Dermatology, University of Naples Federico II, Naples, Italy (3) Department of Advanced Biomedical Sciences, Chair of Forensic Medicine, University of Naples Federico II, Naples, Italy (4) Research Unit Dermatopathology, Department of Dermatology, Medical University of Graz, Austria
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Correspondence to Massimo Mascolo, MD, PhD Department of Advanced Biomedical Sciences, Pathology Section University of Naples Federico II Via Pansini, 5 80131, Naples, Italy E-mail: [email protected]
References 1
Zhang Y, McNutt NS. Lichen striatus. Histological, immunohistochemical, and ultrastructural study of 37 cases. J Cutan Pathol 2001; 28: 65–71. 2 Patrizi A, Neri I, Fiorentini CB et al. Lichen striatus: clinical and laboratory features of 115 children. Pediatr Dermatol 2004; 21: 197–204. 3 Litvinov IV, Jafarian F. Images in clinical medicine. Lichen striatus and lines of Blaschko. N Engl J Med 2012; 25: 2427. 4 Happle R. Genetic interpretation of linear skin abnormalities. Hautarzt 1978; 29: 357–63. 5 Feely MA, Silverberg NB. Two Cases of Lichen Striatus with Prolonged Active Phase. Pediatr Dermatol 2014; 31: e67–68. 6 Cerroni L, Gatter K, Kerl K. Mycosis Fungoides. In: Skin Lymphoma: The Illustrated Guide. London, UK: Wiley-Blackwell, 2009: 11–56. 7 El-Shabrawi-Caelen L, Cerroni L, Medeiros LJ et al. Hypopigmented mycosis fungoides: frequent expression of a CD8+ T-cell phenotype. Am J SurgPathol 2002; 26: 450–7. 8 Jang JG, Sim HG, Kim SH et al. Mycosis fungoides mimicking inflammatory linear verrucous epidermal nevus. JEADV 2004; 18: 218–20. 9 Whittam LR, Calonje E, Orchard G et al. CD8-positive juvenile onset mycosis fungoides: an immunohistochemical and genotypic analysis of six cases. Br J Dermatol 2000; 143: 1199–2204. 10 Möbs M, Cerroni L, Flaig MJ et al. Molecular diagnostics in cutaneous lymphomas. J Dtsch Dermatol Ges 2013; 11: 25–35. 11 Reddy K, Bhawan J. Histologic mimickers of Mycosis Fungoides: a review. J Cutan Pathol 2007; 34: 519–25.
© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1211
Clinical Letter Lichen striatus histopathologically mimicking mycosis fungoides
DOI: 10.1111/ddg.12408
Dear Editors, A skin biopsy taken from the right arm of a 1-year-old girl was submitted with very limited clinical information and no pictures. The biopsy revealed a dense band-like infiltrate composed mainly of small and medium-sized lymphocytes within
a slightly fibrotic papillary dermis, associated with prominent exocytosis of lymphocytes, some of which aligned along the basal membrane, and with presence of intra-epidermal vesicles (Figure 1a–c). The infiltrate involved the mid and deep dermis, forming lymphoid nodules located mainly around hair follicles and eccrine glands, and only focally extended to the subcutaneous tissue. The lymphocytes were positive for CD2, CD3 (Figure 1d–f), CD5, and CD7, with a prevalence of CD8+ cytotoxic T cells compared to CD4+ helper T cells. Loss of T-cell antigens (CD2, CD3, CD5) was not observed. The deep nodular lymphoid infiltrate contained large clusters of B cells. In addition, a focal positivity for CD1a (Figure 1g–i) and negativity for CD117 were observed. A provisional diagnosis of cutaneous lymphoproliferative disorder/suspicion of
Figure 1 Biopsy revealed a band-like lymphocytic infiltrate in the upper dermis and a dense perifollicular infiltrates of lymphocytes in the medium and deep dermis (H&E, 25 x) (a); thickened epidermis, with prominent lymphocytic exocytosis and vesiculation coupled with a band-like infiltrate of lymphocytes in the papillary dermis (H&E, 100 x) (b); prominent lymphocytic exocytosis and small vesicles (H&E, 200 x) (c); immunostaining for CD3 highlighted the predominance of T cells (CD3, 25 x) (d); band-like subepidermal infiltrate composed mainly of T cells (CD3, 100 x) (e); marked exocytosis of T cells (CD3, 200 x) (f); immunostaining for CD1a showed the presence of several Langerhans cells (g: CD1a, 25 x; h: CD1a, 100 x) (g–h); some Langerhans cells within epidermal vesicles (CD1a, 200 x) (i).
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© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1211
Correspondence Clinical Letter
Figure 2 1-year-old girl with erythematous papules arranged in a linear distribution expanding to form a long band (a); details of the papules (b).
mycosis fungoides (MF) was made. The need for a close correlation with the clinical history and appearance of the lesions was mentioned in the histologic report. In the meantime, the child was referred to our clinic. She had small pruritic papules, from 0.5 to 1.5 cm in diameter, arranged to form a long band on her arm (Figure 2a–b). She was otherwise well. The clinical features were sufficiently characteristic to allow a definitive diagnosis of lichen striatus (LS) with unusual dense inflammatory infiltrates. This diagnosis was confirmed by an expert external dermatopathologist (LC). T-cell receptor (TCR) gene rearrangement analysis was made. It resulted in a polyclonal pattern. The patient was followed-up every three months and only after 18 months the lesion showed signs of resolution.
Discussion LS is a rare self-limiting inflammatory disorder predominantly of arms, legs and shoulders that occurs particularly in children [1, 2]. It presents as multiple papules, mostly asymptomatic, arranged linearly along the lines of Blaschko [3]. Most cases resolve spontaneously within a few months; few cases with a prolonged phase of activity may persist for two to three years before resolution [4]. Although it should be distinguished clinically from linear nevi and other chronic inflammatory dermatosis following the lines of Blaschko, including psoriasis, lupus erythematous and morphea, the diagnosis generally relies on clear-cut clinical presentation [5]. However, a skin biopsy may rarely be required in unclear cases. Histology is usually non-diagnostic, showing a mild band-like inflammatory infiltrate of lymphocytes
and histiocytes within the papillary dermis with epidermal acanthosis and parakeratosis, and exocytosis of lymphocytes [1]. The infiltrate may be quite dense and distributed around eccrine glands and vessels. Small intraepidermal vesicles containing lymphocytes and Langerhans cells may be present. Sometimes these lesions may display striking overlapping histopathologic features with lichen nitidus, lichen planus, lichen aureus, lichenoid drug eruptions and MF. In children, MF shows more frequently hypopigmented or pityriasis lichenoides-like lesion, but rarely can present as a linear eruption [6–8]. Histopathologically MF is characterized by the presence of a band-like infiltrate within the papillary dermis, composed of monomorphous lymphoid cells with a different degree of atypia. On many occasions, in early patch MF, small lymphocytes predominate and atypical cells are uncommonly seen [6]. Epidermotropism of lymphocytes can be observed in different forms, including lymphocytes aligned along the basal layer of the epidermis and the formation of Pautrier microabscesses [6]. Neoplastic lymphocytes in MF generally show a CD3+ CD4+, CD8- phenotype [6]. Loss of pan-T markers expression can be observed, but it is very rare in early MF [6]. However, especially in pediatric MF a prevalence of CD8+ cytotoxic T-cells represents a common finding [6, 9]. In our patient, the presence of a dense, band-like infiltrate with prominent exocytosis of lymphocytes with a CD8+ phenotype led to a provisional diagnosis of MF, and a confident diagnosis of LS could be made only upon correlation with the clinical picture. TCR gene rearrangement analysis result was in agreement with the diagnosis of benign inflammatory disorder [10].
© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1211
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Correspondence Clinical Letter
LS may present several overlapping histopathologic features with MF [11], and at times the two conditions may be indistinguishable. The band-like infiltrate with intra-epidermal collections of CD8+ cells, and the lymphoid infiltrate around the follicles within the mid-dermis were erroneously interpreted as features of cytotoxic MF. Although MF may exceptionally present with a linear eruption of small vesicles, in our case the typical clinical presentation and absence of other manifestations of the disease at follow-up allow making a confident diagnosis of LS. We find this case of LS instructive because of the remarkable histopathological similarities to MF and the prolonged phase of activity, representing pitfalls in the clinicopathologic diagnosis. The knowledge of the broad spectrum of histopathologic presentation of LS is essential in dermatopathological practice, especially to exclude a diagnosis of MF. As a general rule, a diagnosis of MF in children should be made, particularly in children, only by integration of complete clinical information and pictures, and morphologic and phenotypic studies, supplemented, in more ambiguous lymphoid proliferation, by molecular approaches; a misdiagnosis, particularly in this age group, may be associated with unnecessary aggressive treatment and disastrous consequences for the patients. Conflict of interest None.
Massimo Mascolo1, Daniela Russo1, Massimiliano Scalvenzi2, Pierpaolo Di Lorenzo3, Lorenzo Cerroni4 (1) Department of Advanced Biomedical Sciences, Pathology Section, University of Naples Federico II, Naples, Italy (2) Department of Dermatology, University of Naples Federico II, Naples, Italy (3) Department of Advanced Biomedical Sciences, Chair of Forensic Medicine, University of Naples Federico II, Naples, Italy (4) Research Unit Dermatopathology, Department of Dermatology, Medical University of Graz, Austria
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Correspondence to Massimo Mascolo, MD, PhD Department of Advanced Biomedical Sciences, Pathology Section University of Naples Federico II Via Pansini, 5 80131, Naples, Italy E-mail: [email protected]
References 1
Zhang Y, McNutt NS. Lichen striatus. Histological, immunohistochemical, and ultrastructural study of 37 cases. J Cutan Pathol 2001; 28: 65–71. 2 Patrizi A, Neri I, Fiorentini CB et al. Lichen striatus: clinical and laboratory features of 115 children. Pediatr Dermatol 2004; 21: 197–204. 3 Litvinov IV, Jafarian F. Images in clinical medicine. Lichen striatus and lines of Blaschko. N Engl J Med 2012; 25: 2427. 4 Happle R. Genetic interpretation of linear skin abnormalities. Hautarzt 1978; 29: 357–63. 5 Feely MA, Silverberg NB. Two Cases of Lichen Striatus with Prolonged Active Phase. Pediatr Dermatol 2014; 31: e67–68. 6 Cerroni L, Gatter K, Kerl K. Mycosis Fungoides. In: Skin Lymphoma: The Illustrated Guide. London, UK: Wiley-Blackwell, 2009: 11–56. 7 El-Shabrawi-Caelen L, Cerroni L, Medeiros LJ et al. Hypopigmented mycosis fungoides: frequent expression of a CD8+ T-cell phenotype. Am J SurgPathol 2002; 26: 450–7. 8 Jang JG, Sim HG, Kim SH et al. Mycosis fungoides mimicking inflammatory linear verrucous epidermal nevus. JEADV 2004; 18: 218–20. 9 Whittam LR, Calonje E, Orchard G et al. CD8-positive juvenile onset mycosis fungoides: an immunohistochemical and genotypic analysis of six cases. Br J Dermatol 2000; 143: 1199–2204. 10 Möbs M, Cerroni L, Flaig MJ et al. Molecular diagnostics in cutaneous lymphomas. J Dtsch Dermatol Ges 2013; 11: 25–35. 11 Reddy K, Bhawan J. Histologic mimickers of Mycosis Fungoides: a review. J Cutan Pathol 2007; 34: 519–25.
© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1211
